Studies recently completed in our laboratories showed that hypothyroid rats have higher serum PRL levels than euthyroid controls yet the pituitaries from these hypothyroid animals demonstrated a decreased ability to synthesize PRL in vitro. This observation is consistent with the concept that the clearance of pituitary prolactin is decreased in hypothyroid animals. In order to test this hypothesis we plan to follow the clearance of serum prolactin from animals in different thyroid states in the following manner. Rats are implanted with the prolactin growth hormone producing MtTW-15 tumor. After initial tumor growth is established the animals will be made hypothyroid (propylthiouracil in their drinking water) or hyperthyroid (excess T4 in their drinking water). When the animals have been maintained for several weeks in their respective thyroid states the pituitary tumor will be surgically removed and the fall in serum prolactin monitored by venous samples drawn at 20 minute intervals. The high levels of prolactin obtained in these animals should allow easy monitoring of the changes in serum prolactin and comparison of the different treatment groups. Preliminary studies in our labs have indicated that rats on I deficient vitamin fortified diet had an increased number and size of mammary tumors following treatment with a carcinogen, NwU, when compared to control animals on a standard lab diet. We plan to pursue this observation further by examining tumor development in the following groups (1) Iodine deficient diet, (2) the same diet as (1) with I (1.6 ppm) added, (3) Iodine deficient diet plus vitamins, (4) the same diet as (3) with I (1.6 ppm) added, and (5) a standard lab diet. This should help identify to what extent Iodine deficiency may be contributory to mammary tumorigenesis. Assuming that specific differences in tumor growth can be identified, the mechanism responsible for this will be sought by carefully evaluating changes in thyroid and pituitary function (serum PRL, TSH, T3, T4 and in vitro pituitary synthesis). BIBLIOGRAPHIC REFERENCE: Augustine, E.C. & R.M. MacLeod. Prolactin and Growth Hormone Synthesis: Effects of Perphenazine, alpha-Methyltyrosine and Estrogen in Different Thyroid States. Proc. Soc. Exp. Biol. Med. 150, 551-556, 1975.